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Q9WTX4

- NRG4_MOUSE

UniProt

Q9WTX4 - NRG4_MOUSE

Protein

Pro-neuregulin-4, membrane-bound isoform

Gene

Nrg4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors.1 Publication

    Keywords - Molecular functioni

    Growth factor

    Enzyme and pathway databases

    ReactomeiREACT_188191. Signaling by ERBB2.
    REACT_188528. GRB2 events in ERBB2 signaling.
    REACT_188574. SHC1 events in ERBB2 signaling.
    REACT_188579. Signaling by ERBB4.
    REACT_188580. SHC1 events in ERBB4 signaling.
    REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198574. Nuclear signaling by ERBB4.
    REACT_203296. PI3K events in ERBB4 signaling.
    REACT_215348. PI3K events in ERBB2 signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pro-neuregulin-4, membrane-bound isoform
    Short name:
    Pro-NRG4
    Cleaved into the following chain:
    Neuregulin-4
    Short name:
    NRG-4
    Gene namesi
    Name:Nrg4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:1933833. Nrg4.

    Subcellular locationi

    Chain Pro-neuregulin-4, membrane-bound isoform : Cell membrane By similarity; Single-pass type I membrane protein By similarity
    Note: Does not seem to be active.By similarity

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 115115Pro-neuregulin-4, membrane-bound isoformPRO_0000019487Add
    BLAST
    Chaini1 – 6161Neuregulin-4PRO_0000019488Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi9 ↔ 23PROSITE-ProRule annotation
    Disulfide bondi17 ↔ 34PROSITE-ProRule annotation
    Disulfide bondi36 ↔ 45PROSITE-ProRule annotation
    Glycosylationi39 – 391N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi60 – 601N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.By similarity
    Extensive glycosylation precedes the proteolytic cleavage.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PRIDEiQ9WTX4.

    Expressioni

    Tissue specificityi

    Highly expressed in pancreas; weakly expressed in muscle.

    Gene expression databases

    ArrayExpressiQ9WTX4.
    BgeeiQ9WTX4.
    CleanExiMM_NRG4.
    GenevestigatoriQ9WTX4.

    Interactioni

    Subunit structurei

    Interacts with ERBB4.1 Publication

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000079037.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9WTX4.
    SMRiQ9WTX4. Positions 16-46.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 6262ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini84 – 11532CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei63 – 8321Helical; Note=Internal signal sequenceSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 4642EGF-likePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization By similarity.By similarity
    ERBB receptor binding is elicited entirely by the EGF-like domain.By similarity

    Sequence similaritiesi

    Belongs to the neuregulin family.Curated
    Contains 1 EGF-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG42904.
    GeneTreeiENSGT00390000014815.
    HOGENOMiHOG000113853.
    HOVERGENiHBG006533.
    InParanoidiQ9WTX4.
    KOiK05458.
    OMAiNGGICYM.
    PhylomeDBiQ9WTX4.

    Family and domain databases

    InterProiIPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    [Graphical view]
    SMARTiSM00181. EGF. 1 hit.
    [Graphical view]
    PROSITEiPS00022. EGF_1. 1 hit.
    PS50026. EGF_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 1 isoform i produced by alternative splicing. Align

    Note: At least 3 isoforms may be produced.

    Isoform 1 (identifier: Q9WTX4-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPTDHEQPCG PRHRSFCLNG GICYVIPTIP SPFCRCIENY TGARCEEVFL    50
    PSSSIPSESN LSAAFVVLAV LLTLTIAALC FLCRKGHLQR ASSVQCEISL 100
    VETNNTRTRH SHREH 115
    Length:115
    Mass (Da):12,744
    Last modified:November 1, 1999 - v1
    Checksum:i989A1E376F857B49
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF083067 mRNA. Translation: AAD21874.1.
    CCDSiCCDS52801.1. [Q9WTX4-1]
    RefSeqiNP_114391.1. NM_032002.2. [Q9WTX4-1]
    XP_006511631.1. XM_006511568.1. [Q9WTX4-1]
    XP_006511632.1. XM_006511569.1. [Q9WTX4-1]
    XP_006511633.1. XM_006511570.1. [Q9WTX4-1]
    UniGeneiMm.443874.

    Genome annotation databases

    EnsembliENSMUST00000130158; ENSMUSP00000115247; ENSMUSG00000032311. [Q9WTX4-1]
    ENSMUST00000164721; ENSMUSP00000130929; ENSMUSG00000032311. [Q9WTX4-1]
    GeneIDi83961.
    KEGGimmu:83961.
    UCSCiuc009psf.2. mouse. [Q9WTX4-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF083067 mRNA. Translation: AAD21874.1 .
    CCDSi CCDS52801.1. [Q9WTX4-1 ]
    RefSeqi NP_114391.1. NM_032002.2. [Q9WTX4-1 ]
    XP_006511631.1. XM_006511568.1. [Q9WTX4-1 ]
    XP_006511632.1. XM_006511569.1. [Q9WTX4-1 ]
    XP_006511633.1. XM_006511570.1. [Q9WTX4-1 ]
    UniGenei Mm.443874.

    3D structure databases

    ProteinModelPortali Q9WTX4.
    SMRi Q9WTX4. Positions 16-46.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000079037.

    Proteomic databases

    PRIDEi Q9WTX4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000130158 ; ENSMUSP00000115247 ; ENSMUSG00000032311 . [Q9WTX4-1 ]
    ENSMUST00000164721 ; ENSMUSP00000130929 ; ENSMUSG00000032311 . [Q9WTX4-1 ]
    GeneIDi 83961.
    KEGGi mmu:83961.
    UCSCi uc009psf.2. mouse. [Q9WTX4-1 ]

    Organism-specific databases

    CTDi 145957.
    MGIi MGI:1933833. Nrg4.

    Phylogenomic databases

    eggNOGi NOG42904.
    GeneTreei ENSGT00390000014815.
    HOGENOMi HOG000113853.
    HOVERGENi HBG006533.
    InParanoidi Q9WTX4.
    KOi K05458.
    OMAi NGGICYM.
    PhylomeDBi Q9WTX4.

    Enzyme and pathway databases

    Reactomei REACT_188191. Signaling by ERBB2.
    REACT_188528. GRB2 events in ERBB2 signaling.
    REACT_188574. SHC1 events in ERBB2 signaling.
    REACT_188579. Signaling by ERBB4.
    REACT_188580. SHC1 events in ERBB4 signaling.
    REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198574. Nuclear signaling by ERBB4.
    REACT_203296. PI3K events in ERBB4 signaling.
    REACT_215348. PI3K events in ERBB2 signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Miscellaneous databases

    NextBioi 350830.
    PROi Q9WTX4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9WTX4.
    Bgeei Q9WTX4.
    CleanExi MM_NRG4.
    Genevestigatori Q9WTX4.

    Family and domain databases

    InterProi IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    [Graphical view ]
    SMARTi SM00181. EGF. 1 hit.
    [Graphical view ]
    PROSITEi PS00022. EGF_1. 1 hit.
    PS50026. EGF_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase."
      Harari D., Tzahar E., Romano J., Shelly M., Pierce J.H., Andrews G.C., Yarden Y.
      Oncogene 18:2681-2689(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ERBB4.
      Strain: C57BL/6J.
      Tissue: Liver.

    Entry informationi

    Entry nameiNRG4_MOUSE
    AccessioniPrimary (citable) accession number: Q9WTX4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 107 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3